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Primary Graft Dysfunction

Natalini, Jake G; Diamond, Joshua M
Primary graft dysfunction (PGD) is a form of acute lung injury after transplantation characterized by hypoxemia and the development of alveolar infiltrates on chest radiograph that occurs within 72 hours of reperfusion. PGD is among the most common early complications following lung transplantation and significantly contributes to increased short-term morbidity and mortality. In addition, severe PGD has been associated with higher 90-day and 1-year mortality rates compared with absent or less severe PGD and is a significant risk factor for the subsequent development of chronic lung allograft dysfunction. The International Society for Heart and Lung Transplantation released updated consensus guidelines in 2017, defining grade 3 PGD, the most severe form, by the presence of alveolar infiltrates and a ratio of PaO2:FiO2 less than 200. Multiple donor-related, recipient-related, and perioperative risk factors for PGD have been identified, many of which are potentially modifiable. Consistently identified risk factors include donor tobacco and alcohol use; increased recipient body mass index; recipient history of pulmonary hypertension, sarcoidosis, or pulmonary fibrosis; single lung transplantation; and use of cardiopulmonary bypass, among others. Several cellular pathways have been implicated in the pathogenesis of PGD, thus presenting several possible therapeutic targets for preventing and treating PGD. Notably, use of ex vivo lung perfusion (EVLP) has become more widespread and offers a potential platform to safely investigate novel PGD treatments while expanding the lung donor pool. Even in the presence of significantly prolonged ischemic times, EVLP has not been associated with an increased risk for PGD.
PMID: 34030200
ISSN: 1098-9048
CID: 4958502

Autoantibody Seropositivity and Risk for Interstitial Lung Disease in a Prospective Male-Predominant Rheumatoid Arthritis Cohort of U.S. Veterans

Natalini, Jake G; Baker, Joshua F; Singh, Namrata; Mahajan, Tina D; Roul, Punyasha; Thiele, Geoffrey M; Sauer, Brian C; Johnson, Cheilonda R; Kawut, Steven M; Mikuls, Ted R; England, Bryant R
PMCID:8009007
PMID: 33026891
ISSN: 2325-6621
CID: 4958472

Fellowship Education in Interstitial Lung Disease. A National Survey of Program Directors and Trainees

Natalini, Jake G; Kassutto, Stacey M; Huie, Tristan J; Kreider, Maryl E
PMCID:8015767
PMID: 33870309
ISSN: 2690-7097
CID: 4958492

Association between antinuclear antibody seropositivity and telomere length: a nationwide population-based study

Natalini, Jake G; George, Michael D; Kawut, Steven M; Johnson, Cheilonda R
OBJECTIVES/OBJECTIVE:Telomere shortening is a well-established marker of biological aging. Whether telomere erosion coincides with age-related increases in antinuclear antibody (ANA) seropositivity remains unknown. Our study aimed to determine the association between ANA seropositivity and shortened telomeres among 1999-2002 National Health and Nutrition Examination Survey (NHANES) subjects. METHODS:We performed a cross-sectional analysis of 2,188 NHANES study participants with available ANA and telomere length data. ANA testing was performed using indirect immunofluorescence. Telomere lengths were measured via quantitative polymerase chain reaction methods. Applying appropriate sample weighting techniques, we used univariate and multivariate logistic regression methods to assess the association between shortened telomeres (i.e. lowest decile of the cohort) and ANA seropositivity. RESULTS:ANAs were positive in 322 out of 2,188 (14.7%, 95% CI 13.3-16.3%) individuals. Subjects with shortened telomeres were more likely to be older (p<0.001), male (p=0.005), and have a cancer history (p<0.001). A higher proportion of non-Hispanic white participants (61.6% vs. 49.3%) and a lower proportion of non-Hispanic black participants (7.8% vs. 17.9%) had shortened telomeres (p<0.001). Shortened telomeres were not independently associated with ANA seropositivity (OR 1.48, 95% CI 0.87-2.52, p=0.14). However, female sex (OR 1.91, 95% CI 1.23-2.96, p=0.006), age ≥80 years (OR 2.06, 95% CI 1.08-3.92, p=0.03), and African American race (OR 1.58, 95% CI 1.00-2.51, p=0.05) were independent risk factors for ANA seropositivity. Neither sex nor race modified the relationship between ANA seropositivity and telomere length. CONCLUSIONS:Telomere erosion does not appear to be responsible for age-related increases in the prevalence of ANA seropositivity.
PMCID:7805007
PMID: 32301432
ISSN: 0392-856x
CID: 4958462

Pulmonary Involvement in Sjögren Syndrome

Natalini, Jake G; Johr, Chadwick; Kreider, Maryl
Sjögren syndrome (SS) is a progressive autoimmune disease characterized by dryness, predominantly of the eyes and mouth, caused by chronic lymphocytic infiltration of the lacrimal and salivary glands. Extraglandular inflammation can lead to systemic manifestations, many of which involve the lungs. Studies in which lung involvement is defined as requiring the presence of respiratory symptoms and either radiograph or pulmonary function test abnormalities quote prevalence estimates of 9% to 22%. The most common lung diseases that occur in relation to SS are airways disease and interstitial lung disease. Evidence-based guidelines to inform treatment recommendations for lung involvement are largely lacking.
PMID: 31376889
ISSN: 1557-8216
CID: 4958452

Understanding the determinants of health-related quality of life in rheumatoid arthritis-associated interstitial lung disease

Natalini, Jake G; Swigris, Jeff J; Morisset, Julie; Elicker, Brett M; Jones, Kirk D; Fischer, Aryeh; Collard, Harold R; Lee, Joyce S
RATIONALE:Health-related quality of life (HRQL) is impaired among patients with interstitial lung disease (ILD). Little is understood about HRQL in specific subtypes of ILD. OBJECTIVES:The aim of this study was to characterize and identify clinical determinants of HRQL among patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and compare them to patients with idiopathic pulmonary fibrosis (IPF). METHODS:We identified patients with a diagnosis of RA-ILD and IPF from an ongoing longitudinal cohort of ILD patients. HRQL was measured at their baseline visit using the Short Form Health Survey (SF-36), versions 1 and 2. Regression models were used to characterize and understand the relationship between selected baseline clinical covariates, the physical component score (PCS) and mental component score (MCS) of the SF-36. MEASUREMENTS AND MAIN RESULTS:RA-ILD patients (n = 50) were more likely to be younger and female compared to IPF patients (n = 50). After controlling for age and pulmonary function, RA-ILD patients had a lower HRQL compared to IPF patients, as measured by the PCS (P = 0.03), with significant differences in two of four PCS domains - bodily pain (P < 0.01) and general health (P = 0.01). Clinical covariates most strongly associated with a lower PCS in RA-ILD patients compared to IPF patients were the presence of joint pain or stiffness and dyspnea severity (P < 0.01). Mental and emotional health, as measured by the MCS, was similar between RA-ILD and IPF patients. CONCLUSION:The physical components of HRQL appear worse in RA-ILD patients compared to IPF patients as measured by the PCS of the SF-36. Differences in the PCS of the SF-36 can be explained in part by dyspnea severity and joint symptoms among patients with RA-ILD.
PMCID:5486989
PMID: 28502413
ISSN: 1532-3064
CID: 4958432

An unusual manifestation of diabetic ketoacidosis and acute colonic pseudo-obstruction [Case Report]

Natalini, Jake; Borno, Hala; Jin, Lan; Jensen, Trevor
Patients presenting with diabetic ketoacidosis and acute colonic pseudo-obstruction should undergo a focused evaluation to identify underlying precipitants.
PMCID:5464381
PMID: 28620506
ISSN: 2054-2704
CID: 4958442

Diabetes mellitus is an independent risk for gastroesophageal reflux disease among urban African Americans

Natalini, J; Palit, A; Sankineni, A; Friedenberg, F K
An association between gastroesophageal reflux disease (GERD) and diabetes mellitus (DM) has been reported. Studies have not been population-based and have failed to include a representative sample of African American subjects. The aim of the study was to determine if DM is independently associated with GERD among urban African Americans. Single-center, population-based survey utilizing a complex, stratified sampling design. To obtain a simple random sample of the entire African American community, targeted survey zones and hand-delivered invitations were identified. Participating subjects had to be self-described African American, age ≥18. Surveys were completed at a computer terminal assisted by a research coordinator. Four hundred nineteen subjects (weighted sample size of 21 264 [20 888-23 930]). GERD prevalence was 23.7% (95% confidence interval [CI] 23.2-23.9). GERD prevalence was 41.5 % in those with DM versus 20.6 % for those without (P < 0.001). Those with GERD had DM longer but had lower glycohemoglobin levels. The prevalence of ≥2 DM comorbidities was higher in those with GERD (odds ratio [OR] = 2.06; 95% CI 1.71-2.48). In the final model, age >40, DM, increasing body mass index, harmful drinking, and increasing smoking dependence were independently associated with GERD. For DM, there was significant effect modification by gender. In males, the risk was (OR = 4.63; 95% CI 3.96-5.40), while in females, the risk was markedly attenuated (OR = 1.79; 95% CI 1.61-2.00). Among urban African Americans, there is an independent association between DM and GERD that appears to be stronger in men. More information is needed to understand this association.
PMID: 24641690
ISSN: 1442-2050
CID: 4958512